Elucidation of the mechanisms of allosteric regulation will be studied by solving to atomic resolution the three-dimensional structures of aspartate transcarbamylase, and of its other forms obtained when allosteric inhibitors (e.g. cytidine triphosphate) or activators (e.g. adenosine triphosphate) are bound. Also, the conformation will be studies when a substrate analogue (N-phosphonacetyl-L-aspartate) is bound. These structural studies are accompanied by parallel chemical studied of fragments (e.g. the enzyme with one regulatory dimer missing), pH effects on regulation, modification of active site and regulatory site groups, mutants, and hybrids. Theoretical studies by molecular orbital methods will be carried out on active sites of alpha-chymotrypsin, carboxypeptidase A, triose phosphate isomerase, lysozyme, and probably other enzymes in the presence of small model substrates. Structures of cyclic peptides, including a number of examples containing proline, and including beta-amanitin (a mushroom toxin) will be carried out by X-ray diffraction methods.